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Data\u003C\/h2\u003E\n \n \n \u003Cdiv class=\u0022pane-content\u0022\u003E\n \u003Cdiv class=\u0022elements-frag-data highwire-markup\u0022 id=\u0022fig-data\u0022\u003E\u003Cdiv id=\u0022fig-data-figures\u0022 class=\u0022group frag-figure\u0022\u003E\u003Cdiv class=\u0022fig-data-title-jump clearfix\u0022\u003E\u003Ch3 class=\u0022fig-data-group-title\u0022\u003EFigures\u003C\/h3\u003E\u003Cdiv class=\u0022fig-data-jump-links\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022item-list\u0022\u003E\u003Cul class=\u0022fig-data-list clearfix\u0022 id=\u0022fragments-fig\u0022\u003E\u003Cli class=\u0022first last\u0022\u003E\u003Cdiv class=\u0022element-fig-data clearfix figure-caption\u0022\u003E\u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022fig-expansion\u0022 id=\u0022F1\u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/31\/15\/5554\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Kinetic and molecular models of TRPA1 channels. A, Allosteric model used to explain the TRPA1 activation by agonists and thermal stimulus. Note that when both stimuli are present, the equilibrium constant between closed and open state (L) becomes CF times larger, enhancing the channel activation. Nevertheless, the channel could visit the open states when all sensors are relaxed, typical behavior of an allosteric model. B, Curves of probability versus temperature at different agonist concentrations using the kinetic model in A. An increase of agonist concentration shifts to higher temperatures the T1\/2 value (obtained from Boltzmann equation fits), increasing the open probability of the channel, characteristic of the cold hypersensitivity process. At saturating agonist concentration, the channels become insensitive to cold, because they reach their maximum open probability, previously obtained by del Camino et al. (2010). Their work showed a minimum for TRPA1 channels activation in agonist\u0027s absence. This model fully supports the del Camino et al. (2010) findings. C, Activation mechanism of TRPA1 channel. The binding sites for agonists (orange balls) and the thermal sensors (blue balls) are located in different regions of the protein. They are coupling independently with the opening of the pore. When the extreme cold activates just the thermochannel sensors but their agonist binding sites still are empty, the Ca2+ influx is poor and thus the cold fiber detection is also poor and inadequate to generate action potentials. However, when both stimuli are present (the sensors are activated and the agonists have been binding with the channel), a massive entry of Ca2+ concentration produces a high level of membrane depolarization to result in TRPA1 channels with a dual role of detection in the nociceptive fibers involved with cold hypersensitivity. D, Relative increase of Po in response to temperature decrease from 30 to 10\u0026#x2013;20\u0026#xB0;C at different agonist concentrations. This graphic was generated by our proposed model. It is almost an exact reproduction of Figure 3C from del Camino et al. (2010). Here, del Camino et al. (2010) showed this relationship for the total relative current.\u0022 class=\u0022highwire-fragment fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-992213443\u0022 data-figure-caption=\u0022\u0026lt;div class=\u0026quot;highwire-markup\u0026quot;\u0026gt;Kinetic and molecular models of TRPA1 channels. A, Allosteric model used to explain the TRPA1 activation by agonists and thermal stimulus. Note that when both stimuli are present, the equilibrium constant between closed and open state (L) becomes CF times larger, enhancing the channel activation. Nevertheless, the channel could visit the open states when all sensors are relaxed, typical behavior of an allosteric model. B, Curves of probability versus temperature at different agonist concentrations using the kinetic model in A. An increase of agonist concentration shifts to higher temperatures the T1\/2 value (obtained from Boltzmann equation fits), increasing the open probability of the channel, characteristic of the cold hypersensitivity process. At saturating agonist concentration, the channels become insensitive to cold, because they reach their maximum open probability, previously obtained by del Camino et al. (2010). Their work showed a minimum for TRPA1 channels activation in agonist\u0027s absence. This model fully supports the del Camino et al. (2010) findings. C, Activation mechanism of TRPA1 channel. The binding sites for agonists (orange balls) and the thermal sensors (blue balls) are located in different regions of the protein. They are coupling independently with the opening of the pore. When the extreme cold activates just the thermochannel sensors but their agonist binding sites still are empty, the Ca2+ influx is poor and thus the cold fiber detection is also poor and inadequate to generate action potentials. However, when both stimuli are present (the sensors are activated and the agonists have been binding with the channel), a massive entry of Ca2+ concentration produces a high level of membrane depolarization to result in TRPA1 channels with a dual role of detection in the nociceptive fibers involved with cold hypersensitivity. D, Relative increase of Po in response to temperature decrease from 30 to 10\u0026#x2013;20\u0026#xB0;C at different agonist concentrations. This graphic was generated by our proposed model. It is almost an exact reproduction of Figure 3C from del Camino et al. (2010). Here, del Camino et al. (2010) showed this relationship for the total relative current.\u0026lt;\/div\u0026gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cspan class=\u0022hw-responsive-img\u0022\u003E\u003Cimg class=\u0022highwire-fragment fragment-image lazyload\u0022 alt=\u0022Figure 1.\u0022 src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 data-src=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/31\/15\/5554\/F1.medium.gif\u0022 width=\u0022440\u0022 height=\u0022368\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-fragment fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/31\/15\/5554\/F1.medium.gif\u0022 width=\u0022440\u0022 height=\u0022368\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u0022download-fig first\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/31\/15\/5554\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022new-tab\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/31\/15\/5554\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022download-ppt last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/529545\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \u003Cp id=\u0022p-5\u0022\u003EKinetic and molecular models of TRPA1 channels. \u003Cstrong\u003E\u003Cem\u003EA\u003C\/em\u003E\u003C\/strong\u003E, Allosteric model used to explain the TRPA1 activation by agonists and thermal stimulus. Note that when both stimuli are present, the equilibrium constant between closed and open state (\u003Cem\u003EL\u003C\/em\u003E) becomes CF times larger, enhancing the channel activation. Nevertheless, the channel could visit the open states when all sensors are relaxed, typical behavior of an allosteric model. \u003Cstrong\u003E\u003Cem\u003EB\u003C\/em\u003E\u003C\/strong\u003E, Curves of probability versus temperature at different agonist concentrations using the kinetic model in \u003Cstrong\u003E\u003Cem\u003EA\u003C\/em\u003E\u003C\/strong\u003E. An increase of agonist concentration shifts to higher temperatures the \u003Cem\u003ET\u003C\/em\u003E\u003Csub\u003E1\/2\u003C\/sub\u003E value (obtained from Boltzmann equation fits), increasing the open probability of the channel, characteristic of the cold hypersensitivity process. At saturating agonist concentration, the channels become insensitive to cold, because they reach their maximum open probability, previously obtained by \u003Ca id=\u0022xref-ref-2-6\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-2\u0022\u003Edel Camino et al. (2010)\u003C\/a\u003E. Their work showed a minimum for TRPA1 channels activation in agonist\u0027s absence. This model fully supports the \u003Ca id=\u0022xref-ref-2-7\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-2\u0022\u003Edel Camino et al. (2010)\u003C\/a\u003E findings. \u003Cstrong\u003E\u003Cem\u003EC\u003C\/em\u003E\u003C\/strong\u003E, Activation mechanism of TRPA1 channel. The binding sites for agonists (orange balls) and the thermal sensors (blue balls) are located in different regions of the protein. They are coupling independently with the opening of the pore. When the extreme cold activates just the thermochannel sensors but their agonist binding sites still are empty, the Ca\u003Csup\u003E2+\u003C\/sup\u003E influx is poor and thus the cold fiber detection is also poor and inadequate to generate action potentials. However, when both stimuli are present (the sensors are activated and the agonists have been binding with the channel), a massive entry of Ca\u003Csup\u003E2+\u003C\/sup\u003E concentration produces a high level of membrane depolarization to result in TRPA1 channels with a dual role of detection in the nociceptive fibers involved with cold hypersensitivity. \u003Cstrong\u003E\u003Cem\u003ED\u003C\/em\u003E\u003C\/strong\u003E, Relative increase of \u003Cem\u003EP\u003C\/em\u003E\u003Csub\u003Eo\u003C\/sub\u003E in response to temperature decrease from 30 to 10\u201320\u00b0C at different agonist concentrations. This graphic was generated by our proposed model. It is almost an exact reproduction of \u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/30\/45\/15165\/F3\u0022\u003EFigure 3\u003Cem\u003EC\u003C\/em\u003E\u003C\/a\u003E from \u003Ca id=\u0022xref-ref-2-8\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-2\u0022\u003Edel Camino et al. (2010)\u003C\/a\u003E. Here, \u003Ca id=\u0022xref-ref-2-9\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-2\u0022\u003Edel Camino et al. (2010)\u003C\/a\u003E showed this relationship for the total relative current.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E \u003C\/div\u003E\n\n \n \u003C\/div\u003E\n\u003Cdiv class=\u0022panel-separator\u0022\u003E\u003C\/div\u003E\u003Cdiv class=\u0022panel-pane pane-earthchem\u0022 \u003E\n \n \n \n \u003Cdiv class=\u0022pane-content\u0022\u003E\n \u003Ca href=\u0022http:\/\/ecp.iedadata.org\/doidata\/10.1523\/JNEUROSCI.6775-10.2011\u0022 class=\u0022\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg src=\u0022http:\/\/ecp.iedadata.org\/doibanner\/10.1523\/JNEUROSCI.6775-10.2011\u0022 alt=\u0022\u0022 \/\u003E\u003C\/a\u003E \u003C\/div\u003E\n\n \n \u003C\/div\u003E\n\u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/www.jneurosci.org\/sites\/default\/files\/js\/js_hZg96SP9gBcOluDp2mGc57d8sP8uJ7g8P_JYsCISOgQ.js\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}